Cancer Immunotherapy Using Artificial Adjuvant Vector Cells to Deliver NY-ESO-1 Antigen to Dendritic Cells in Situ

Overview

Journal Cancer Sci

Specialty Oncology

Date 2021 Dec 31

PMID 34971473

Citations 8

Authors

Shin-Ichiro Fujii

Satoru Yamasaki

Kenichi Hanada

Shogo Ueda

Masami Kawamura

Kanako Shimizu

Affiliations

Soon will be listed here.

Abstract

NY-ESO-1 is a cancer/testis antigen expressed in various cancer types. However, the induction of NY-ESO-1-specific CTLs through vaccines is somewhat difficult. Thus, we developed a new type of artificial adjuvant vector cell (aAVC-NY-ESO-1) expressing a CD1d-NKT cell ligand complex and a tumor-associated antigen, NY-ESO-1. First, we determined the activation of invariant natural killer T (iNKT) and natural killer (NK) cell responses by aAVC-NY-ESO-1. We then showed that the NY-ESO-1-specific CTL response was successfully elicited through aAVC-NY-ESO-1 therapy. After injection of aAVC-NY-ESO-1, we found that dendritic cells (DCs) in situ expressed high levels of costimulatory molecules and produced interleukn-12 (IL-12), indicating that DCs undergo maturation in vivo. Furthermore, the NY-ESO-1 antigen from aAVC-NY-ESO-1 was delivered to the DCs in vivo, and it was presented on MHC class I molecules. The cross-presentation of the NY-ESO-1 antigen was absent in conventional DC-deficient mice, suggesting a host DC-mediated CTL response. Thus, this strategy helps generate sufficient CD8 NY-ESO-1-specific CTLs along with iNKT and NK cell activation, resulting in a strong antitumor effect. Furthermore, we established a human DC-transferred NOD/Shi-scid/IL-2γc immunodeficient mouse model and showed that the NY-ESO-1 antigen from aAVC-NY-ESO-1 was cross-presented to antigen-specific CTLs through human DCs. Taken together, these data suggest that aAVC-NY-ESO-1 has potential for harnessing innate and adaptive immunity against NY-ESO-1-expressing malignancies.

Citing Articles

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References

Valmori D, Souleimanian N, Tosello V, Bhardwaj N, Adams S, ONeill D . Vaccination with NY-ESO-1 protein and CpG in Montanide induces integrated antibody/Th1 responses and CD8 T cells through cross-priming. Proc Natl Acad Sci U S A. 2007; 104(21):8947-52. PMC: 1885608. DOI: 10.1073/pnas.0703395104. View

Shimizu K, Kurosawa Y, Taniguchi M, Steinman R, Fujii S . Cross-presentation of glycolipid from tumor cells loaded with alpha-galactosylceramide leads to potent and long-lived T cell mediated immunity via dendritic cells. J Exp Med. 2007; 204(11):2641-53. PMC: 2118481. DOI: 10.1084/jem.20070458. View

Jungbluth A, Antonescu C, Busam K, Iversen K, Kolb D, Coplan K . Monophasic and biphasic synovial sarcomas abundantly express cancer/testis antigen NY-ESO-1 but not MAGE-A1 or CT7. Int J Cancer. 2001; 94(2):252-6. DOI: 10.1002/ijc.1451. View

Motohashi S, Nagato K, Kunii N, Yamamoto H, Yamasaki K, Okita K . A phase I-II study of alpha-galactosylceramide-pulsed IL-2/GM-CSF-cultured peripheral blood mononuclear cells in patients with advanced and recurrent non-small cell lung cancer. J Immunol. 2009; 182(4):2492-501. DOI: 10.4049/jimmunol.0800126. View

Iyoda T, Yamasaki S, Hidaka M, Kawano F, Abe Y, Suzuki K . Amelioration of NK cell function driven by Vα24 invariant NKT cell activation in multiple myeloma. Clin Immunol. 2017; 187:76-84. DOI: 10.1016/j.clim.2017.10.007. View

Fujii S, Shimizu K, Kronenberg M, Steinman R . Prolonged IFN-gamma-producing NKT response induced with alpha-galactosylceramide-loaded DCs. Nat Immunol. 2002; 3(9):867-74. DOI: 10.1038/ni827. View

Watanabe Y, Takahashi T, Okajima A, Shiokawa M, Ishii N, Katano I . The analysis of the functions of human B and T cells in humanized NOD/shi-scid/gammac(null) (NOG) mice (hu-HSC NOG mice). Int Immunol. 2009; 21(7):843-58. DOI: 10.1093/intimm/dxp050. View

Griffiths E, Srivastava P, Matsuzaki J, Brumberger Z, Wang E, Kocent J . NY-ESO-1 Vaccination in Combination with Decitabine Induces Antigen-Specific T-lymphocyte Responses in Patients with Myelodysplastic Syndrome. Clin Cancer Res. 2017; 24(5):1019-1029. PMC: 5844797. DOI: 10.1158/1078-0432.CCR-17-1792. View

Wherry E, Kurachi M . Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol. 2015; 15(8):486-99. PMC: 4889009. DOI: 10.1038/nri3862. View

10.

Schumacher T, Schreiber R . Neoantigens in cancer immunotherapy. Science. 2015; 348(6230):69-74. DOI: 10.1126/science.aaa4971. View

11.

Fujii S, Yamasaki S, Hanada K, Ueda S, Kawamura M, Shimizu K . Cancer immunotherapy using artificial adjuvant vector cells to deliver NY-ESO-1 antigen to dendritic cells in situ. Cancer Sci. 2021; 113(3):864-874. PMC: 8898705. DOI: 10.1111/cas.15259. View

12.

Odunsi K, Qian F, Matsuzaki J, Mhawech-Fauceglia P, Andrews C, Hoffman E . Vaccination with an NY-ESO-1 peptide of HLA class I/II specificities induces integrated humoral and T cell responses in ovarian cancer. Proc Natl Acad Sci U S A. 2007; 104(31):12837-42. PMC: 1937553. DOI: 10.1073/pnas.0703342104. View

13.

Kumai T, Kobayashi H, Harabuchi Y, Celis E . Peptide vaccines in cancer-old concept revisited. Curr Opin Immunol. 2016; 45:1-7. PMC: 5449210. DOI: 10.1016/j.coi.2016.11.001. View

14.

Chen Q, Jackson H, Parente P, Luke T, Rizkalla M, Tai T . Immunodominant CD4+ responses identified in a patient vaccinated with full-length NY-ESO-1 formulated with ISCOMATRIX adjuvant. Proc Natl Acad Sci U S A. 2004; 101(25):9363-8. PMC: 438982. DOI: 10.1073/pnas.0403271101. View

15.

Lee Y, Wang H, Starrett G, Phuong V, Jameson S, Hogquist K . Tissue-Specific Distribution of iNKT Cells Impacts Their Cytokine Response. Immunity. 2015; 43(3):566-78. PMC: 4575275. DOI: 10.1016/j.immuni.2015.06.025. View

16.

Carreno B, Magrini V, Becker-Hapak M, Kaabinejadian S, Hundal J, Petti A . Cancer immunotherapy. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells. Science. 2015; 348(6236):803-8. PMC: 4549796. DOI: 10.1126/science.aaa3828. View

17.

Davis I, Chen W, Jackson H, Parente P, Shackleton M, Hopkins W . Recombinant NY-ESO-1 protein with ISCOMATRIX adjuvant induces broad integrated antibody and CD4(+) and CD8(+) T cell responses in humans. Proc Natl Acad Sci U S A. 2004; 101(29):10697-702. PMC: 489997. DOI: 10.1073/pnas.0403572101. View

18.

Sharma P, Bajorin D, Jungbluth A, Herr H, Old L, Gnjatic S . Immune responses detected in urothelial carcinoma patients after vaccination with NY-ESO-1 protein plus BCG and GM-CSF. J Immunother. 2008; 31(9):849-57. DOI: 10.1097/CJI.0b013e3181891574. View

19.

Andre P, Denis C, Soulas C, Bourbon-Caillet C, Lopez J, Arnoux T . Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells. Cell. 2018; 175(7):1731-1743.e13. PMC: 6292840. DOI: 10.1016/j.cell.2018.10.014. View

20.

Shimizu K, Goto A, Fukui M, Taniguchi M, Fujii S . Tumor cells loaded with alpha-galactosylceramide induce innate NKT and NK cell-dependent resistance to tumor implantation in mice. J Immunol. 2007; 178(5):2853-61. DOI: 10.4049/jimmunol.178.5.2853. View